PROJECT SUMMARY/ABSTRACT This proposal is responsive to PA-16-161. In 2010, ~6.1 million Americans had a diagnosis of atrial fibrillation (AF), a number projected to rise to more than 12 million by 2050. The prevalence of AF increases with age, reaching a prevalence of 9% among adults over 80 years. In nursing homes (NHs), the prevalence of AF is 17%. The risk for ischemic stroke is increased 5-fold among patients with AF. In clinical trials, anticoagulation with vitamin K antagonists (VKAs) has been demonstrated to reduce ischemic stroke risk in high risk patients with AF by 65% compared with placebo. VKAs have a narrow therapeutic range and departures from the therapeutic range have large implications for the risk of thromboembolic and bleeding events. Although essentially all NH residents meet the high risk definition (CHA2DSs-Vasc >2) where anticoagulation is recommended, fewer than half of residents have been treated historically. VKA management in the NH has been a challenge, with half of the time on treatment outside of the therapeutic range. The pharmacologic management of AF has transformed in recent years with the approval of 4 direct-acting oral anticoagulants (DOACs) since 2010. The DOACs are comparable to VKAs in safety and efficacy, but typically do not require strict monitoring. These alternative therapeutic options have rapidly displaced VKAs in AF and have expanded the number of community dwelling patients receiving anticoagulation. The use of DOACs in NHs and the contemporary utilization of VKAs in NHs has not been evaluated. NH residents often have severe cognitive and functional deficits, along with a high burden of polypharmacy and multimorbidity. Meaningful outcomes for this population (e.g., preservation of cognitive and physical functioning) are often not studied in clinical trials. More than 7 million US adults will use NH services by 2040. Evidence is needed to guide anticoagulation practices for AF specific to this expanding, clinically complex population. Using contemporaneous, national federally-mandated Minimum Data Set 3.0 linked to Medicare Part A and D claims, the aims are to: 1) determine contemporary VKA and DOAC utilization rates in a NH population; 2.) compare the incidence of 1-year safety (i.e., bleeding) and effectiveness (i.e., thromboembolism) outcomes between anticoagulated and untreated NH residents and by anticoagulant type (VKA versus DOACs); 3.) identify the characteristics (e.g., cognitive and physical impairments, fall risk, additional comorbidities) of NH residents with AF for whom anticoagulation confers a net clinical benefit. By expanding the evidence base to inform AF treatment decisions for the prevention of a debilitating disease (i.e., stroke) in an aged nursing home population, this proposal addresses the Stroke Prevention Research Priority of the National Institute of Neurological Disorders and Stroke and Strategic Goal C of the National Institute on Aging.